The Therapeutic Effect of STAT3 Signaling-Suppressed MSC on Pain and Articular Cartilage Damage in a Rat Model of Monosodium Iodoacetate-Induced Osteoarthritis

Osteoarthritis (OA) is a degenerative disease that induces pain, cartilage deformation, and joint inflammation. Mesenchymal stem cells (MSCs) are potential therapeutic agents for treatment of OA. However, MSC therapy can cause excessive inflammation. Signal transducer and activator of transcription 3 (STAT3) modulates secretion of many proinflammatory cytokines. Experimental OA was induced by intra-articular (IA) injection of monosodium iodoacetate (MIA) to the right knee of rats. MSCs from OA patients (OA-MSCs) were treated with STA21, a small molecule that blocks STAT3 signaling, by IA or intravenous (IV) injection after MIA injection. Pain severity was quantified by assessment of secondary tactile allodynia using the von Frey assessment test. Cartilage degradation was measured by microcomputed tomography image analysis, histological analysis, and the Mankin score. Protein and gene expression was evaluated by enzyme-linked immunosorbent assay, immunohistochemistry, and real-time polymerase chain reaction. MSCs increased production of proinflammatory cytokines under inflammatory conditions. STA21 significantly decreased expression of these proinflammatory molecules via inhibition of STAT3 activity but increased gene expression of molecules related to migration potential and immunomodulation in OA-MSCs. STAT3-inhibited OA-MSCs administrated by IV or IA injection decreased pain severity and cartilage damage in rats with MIA-induced OA rats by decreasing proinflammatory cytokines in the joints. Combined IA and IV-injected STAT3-inhibited OA-MSCs had an additive effect of pain relief in MIA-induced OA rats. STAT3 inhibition may optimize the therapeutic activities of MSCs for treating OA by attenuating pain and progression of MIA by inhibiting inflammation and cartilage damage

Determinants of Working Practice Location for Clinicians According to High School, Medical School, and Resident Training Locations in Korea

Although several regulations have been implemented for medical school admission, such as a quota system, the uneven distribution of healthcare personnel across regions is an unresolved problem in Korea. This study explores the distribution and retention rate of clinicians across regions according to the degree of experience staying in the current clinical area during high school/medical school/resident training using 2016 Korean Physician Survey data. Both in metropolitan and non-metropolitan areas, clinicians who completed high school, medical school, and resident training in the current practice region (Subgroup D) accounted for the largest proportion (Metro, n = 1611, 46.1%; non-metro, n = 1917, 52.9%). The retention rate was the highest in Subgroup D both in metropolitan (84.3%) and non-metropolitan areas (Chungcheong 86.2%, Jeolla 79.9%, Daegu/Gyeongbuk 81.6%, Busan/Ulsan/Gyeongnam 93.3%) except Gangwon and Jeju. The second, third, and fourth highest retention rates were observed in cases where clinicians completed their high school and resident training, medical school and resident training, and resident training only, respectively, in all regions, although the ranking differs by region. To increase the retention rate of physicians, this study shows that it is necessary for a student to seek ways to continue training in the same region in which they graduated from medical school

Enteroviruses isolated from herpangina and hand-foot-and-mouth disease in Korean children

Abstract Hand-foot-and-mouth disease (HFMD) and herpangina are commonly prevalent illness in young children. They are similarly characterized by lesions on the skin and oral mucosa. Both diseases are associated with various enterovirus serotypes. In this study, enteroviruses from patients with these diseases in Korea in 2009 were isolated and analyzed. Demographic data for patients with HFMD and herpangina were compared and all enterovirus isolates were amplified in the VP1 region by reverse transcription-polymerase chain reaction and sequenced. Among the enterovirus isolates, prevalent agents were coxsackievirus A16 in HFMD and coxsackievirus A5 in herpangina. More prevalent months for HFMD were June (69.2%) and May (11.5%), and June (40.0%) and July (24.0%) for herpangina. Age prevalence of HFMD patients with enterovirus infection was 1 year (23.1%), 4 years (19.2%), and over 5 years (19.2%). However, the dominant age group of herpangina patients with enterovirus infection was 1 year (48.0%) followed by 2 years (28.0%). Comparison of pairwise VP1 nucleotide sequence alignment of all isolates within the same serotypes revealed high intra-type variation of CVA2 isolates (84.6–99.3% nucleotide identity). HFMD and herpangina showed differences in demographic data and serotypes of isolated enteroviruses, but there was no notable difference in amino acid sequences by clinical syndromes in multiple comparison of the partial VP1 gene sequence.</p

Co-occurrence of threshold switching and memory switching in Pt/NbOx/Pt cells for crosspoint memory applications

To integrate bipolar resistive switching cells into crosspoint structures, we serially connect a threshold-switching (TS) Pt/NbO2/Pt device with a memory-switching (MS) Pt/Nb2O5/Pt device and observe the suppression of the undesired sneak current. A simpler Pt/Nb2O5/NbO2/Pt bilayer oxide device was designed; it simultaneously exhibits TS and MS. The unique device characteristics in the metal/oxide/metal structure can be directly integrated into a crosspoint memory array without the diode; this can significantly reduce the fabrication complexity

Highly Stretchable, High-Mobility, Free-Standing All-Organic Transistors Modulated by Solid-State Elastomer Electrolytes

Highly stretchable, high-mobility, and free-standing coplanar-type all-organic transistors based on deformable solid-state elastomer electrolytes are demonstrated using ionic thermoplastic polyurethane (i-TPU), thereby showing high reliability under mechanical stimuli as well as low-voltage operation. Unlike conventional ionic dielectrics, the i-TPU electrolyte prepared herein has remarkable characteristics, i.e., a large specific capacitance of 5.5 mu F cm(-2), despite the low weight ratio (20 wt%) of the ionic liquid, high transparency, and even stretchability. These i-TPU-based organic transistors exhibit a mobility as high as 7.9 cm(2) V-1 s(-1), high bendability (R-c, radius of curvature: 7.2 mm), and good stretchability (60% tensile strain). Moreover, they are suitable for low-voltage operation (V-DS = -1.0 V, V-GS = -2.5 V). In addition, the electrical characteristics such as mobility, on-current, and threshold voltage are maintained even in the concave and convex bending state (bending tensile strain of approximate to 3.4%), respectively. Finally, free-standing, fully stretchable, and semi-transparent coplanar-type all-organic transistors can be fabricated by introducing a poly(3,4-ethylenedioxythiophene):polystyrene sulfonic acid layer as source/drain and gate electrodes, thus achieving low-voltage operation (V-DS = -1.5 V, V-GS = -2.5 V) and an even higher mobility of up to 17.8 cm(2) V-1 s(-1). Moreover, these devices withstand stretching up to 80% tensile strain

Filament-type resistive switching in homogeneous Bi-layer Pr0.7Ca0.3MnO3 thin film memory devices

It is known that Pt/ Pr0.7 Ca0.3 Mn O3 (PCMO)/Pt structures show no hysteresis loops in current-voltage curves due to the symmetric top and bottom interfaces. Here, we prepared an asymmetric memory device using bi-layer PCMO thin films with different oxygen content. The repeatable and stable resistive switching is observed. The excellent resistive switching characteristics such as a large RHRS / RLRS (where HRS is the high resistance state and LRS is the low resistance state) ratio (∼1000), sweeping endurance (>100), and long retention time (> 105 s) can be obtained using a bipolar operation mode. It is suggested that the switching process can be elucidated to the formation and rupture of localized conductive filament along with the migration of oxygen ions

Oral Cholera Vaccine Efficacy and Effectiveness

Although measuring vaccine efficacy through the conventional phase III study design, randomized, double-blinded controlled trial serves as the “gold standard”, effectiveness studies, conducted in the context of a public health program, seek to broaden the understanding of the impact of a vaccine in a real world setting including both individual and population level impacts. Cholera is an acute diarrheal infection caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae. Since the 1980s, either killed or live oral cholera vaccines (OCVs) have been developed and efficacy and effectiveness studies have been conducted on OCV. Although the results of OCV effectiveness studies sometimes showed outliers, the tendency seen is for effectiveness of the vaccine used in public health settings to be somewhat higher than estimated in randomized controlled trials due to the influence of indirect herd protection. Efficacy and Effectiveness studies both generate important information about the vaccine performance characteristics and its impact when used in real world populations at risk for the disease

Blood cadmium and volume of uterine fibroids in premenopausal women

Abstract Background A number of studies have found associations between heavy metals and uterine fibroids, but the results are inconsistent. Here, we conducted this research to demonstrate the relationships between blood heavy metal concentrations and uterine fibroid volume as well as the rate of uterine fibroid presence. Methods In a cross-sectional study, we collected data from 308 premenopausal women aged 30–49 years in Seoul; uterine fibroids are ascertained by past history of myomectomy and pelvic ultrasonography. In the analytic phase, we first analyzed the presence of the fibroids and the concentrations of heavy metals via logistic regression. In subgroup analysis, we used simple and multiple linear regression analyses to examine the associations between heavy metals and uterine fibroid volume. Results There was no connection between the heavy metal concentrations and the presence of uterine fibroids, but the odds of women having fibroids were higher with three particular metals. In subgroup analysis, the association between blood cadmium concentrations and uterine fibroid volume was statistically significant (adjusted beta coefficient = 2.22, 95% confidential interval: 0.06–4.37). In contrast, blood mercury and lead concentrations were not significantly associated with uterine fibroid volume. Conclusions Our findings are the first that we know to report the association of blood cadmium concentrations with the volume of uterine fibroids. We expect that our findings will be used as evidence for supporting policies to improve premenopausal Korean women’s health